We have established that pyrroline-5-carboxylate (P5C) is a nutrition-dependent intercellular communicator which modulates the effects of certain growth factors in transmembrane signaling. First, we demonstrated that P5C is a constituent of human plasma and levels of P5C show peaks 15-fold over baseline approximately 2 hrs. following meals. Thus, the physiologic variation in P5C concentrations can transmit nutrient-dependent information to peripheral tissues. The interaction of P5C with cells occurs through a novel mechanism. P5C entry into cells is mediated by a specific, saturable group translocation mechanism which transfers oxidizing potential across cell membranes. This transfer of oxidizing potential initiates a metabolic cascade which sequentially activates the pentose phosphate shunt, stimulates phosphoribosyl pyrophosphate formation and increases ribonucleotide synthesis. P5C reductase plays a role in the group translocation and transfer of oxidizing potential. The enzyme has been purified from human erythrocytes and its kinetic properties defined. From these properties it can be concluded that the enzyme functions as an NADPH oxidase with P5C as electron acceptor. Furthermore, this enzyme is associated with plasma membranes and the transfer of oxidizing potential is regulated by protein-protein interactions. Of special interest, P5C acts synergistically with platelet-derived growth factor in stimulating phosphoribosyl pyrophosphate formation. The mechanism involves the turnover of phosphoinositides and activation of protein kinase C. These studies show that P5C serves as a novel mechanism for integrating nutritional influences with growth factor-stimulated cellular events to produce physiologic or pathophysiologic responses.